A Case of Malignant Brenner Tumor of the Ovary Incidentally Found in a Patient with Deep Vein Thrombosis.

We present the case of a 73-year-old woman who was incidentally found to have a malignant Brenner tumor (MBT) of the ovary during an evaluation for deep vein thrombosis (DVT). The patient presented with swelling in her left leg, non-healing ulcers, weakness, and numbness in her lower limbs. Imaging studies revealed a large multiloculated cystic mass with areas of calcification in the left adnexa extending to the upper abdomen toward the gallbladder fossa. The patient underwent exploratory laparotomy with removal of the ovarian cyst, later diagnosed as a focal MBT in a background of borderline Brenner tumor. Brenner tumors of the ovary are a rare subtype of ovarian neoplasm that accounts for less than 2% of all ovarian tumors. MBTs are even rarer, comprising less than 5% of all Brenner tumors. To our knowledge, this is the first reported case of an MBT incidentally found in a patient with DVT.

Coexistence of malignant ovarian Brenner tumor and borderline mucinous cystadenoma, combined with primary uterine corpus endometrioid carcinoma: A case report and literature review.

Malignant Brenner tumor (MBT) of the ovary is a rare malignant ovarian tumor, whereas uterine corpus endometrioid carcinoma (UEC) constitutes one of the most common malignant tumors of the female reproductive system. The present study reported on a case of the coexistence of ovarian MBT and borderline mucinous cystadenoma combined with primary UEC. Therefore, the present case is a synchronous primary cancer of both ovary and endometrium. Although synchronous primary cancers of the endometrium and ovary are relatively uncommon, they are not rare; however, due to the rarity of MBT, this case was considered singular. To the best of our knowledge, this was the first-ever reported case of the coexistence of an ovarian MBT and borderline mucinous cystadenoma combined with primary UEC. Based on a review of the literature associated with the present case, its clinicopathological features, immunohistochemical phenotype, differential diagnosis, molecular changes, prognosis and treatment were summarized and discussed. The aim of the present study was to improve the understanding of this rare synchronous primary cancer of the ovary and endometrium so as to avoid future misdiagnosis.

MDM2 amplification in malignant Brenner tumors may play a role in progression to malignancy and aid in separation from urothelial and other ovarian carcinomas.

Malignant Brenner tumor (MBT) is diagnosed in the setting of invasive high-grade carcinoma with urothelial-like morphology and the presence of an adjacent benign Brenner tumor (BBT) or borderline Brenner tumor (BLBT). MDM2 amplification was recently detected by next-generation sequencing on a small number of MBTs, potentially significant for future targeted therapy. Experience is limited, however, and evaluation of widely available MDM2 immunohistochemistry (IHC) has not been performed to determine clinical utility. After confirming all diagnoses morphologically and immunohistochemically, we performed MDM2 IHC on 4 MBTs, 3 BLBTs, 26 BBTs, 142 high-grade serous carcinomas (HGSC), 6 ovarian endometrioid carcinomas (OEC) with urothelial-like morphology, and 49 high-grade urothelial carcinomas (HGUC). MDM2 IHC was considered positive with diffuse (>25%) nuclear reactivity; in cases of patchy staining (10-25% nuclear reactivity), MDM2 was considered equivocal. Positive staining in <10% of cells was considered negative. In cases with positive or equivocal staining, MDM2 amplification was evaluated by fluorescence in-situ hybridization (FISH). Three MBTs (75%) showed diffuse nuclear reactivity for MDM2 by IHC, a finding corroborated by amplification of MDM2 in all three cases. One MBT and 2 BLBTs showed equivocal MDM2 IHC, but all three were negative for MDM2 amplification. The final BLBT, as well as all BBTs, HGSC, OEC, and HGUC, were negative for MDM2. In conclusion, our limited cohort confirms MDM2 amplification in MBT and suggests that MDM2 IHC may have an influence in rare diagnostically challenging cases.

Amplification of MDM2 and Loss of p16 Expression: Do They Have a Role in Malignant Transformation of Ovarian Brenner Tumor?

OBJECTIVES: To review the significance of MDM2 and cyclin D1 expression and loss of p16 expression in malignant and borderline Brenner tumors (BTs) of the ovary. METHODS: We describe 2 new cases of ovarian BT, 1 malignant and 1 borderline. We studied MDM2, p16, and cyclin D1 expression by immunohistochemistry in the benign, borderline, and malignant components of these 2 cases and in 5 additional cases of benign BT. We also reviewed and summarized the literature on the clinical, immunohistochemical and molecular characteristics of borderline and malignant BTs (BdBTs and MBTs). RESULTS: Nuclear expression of MDM2 was seen only in the MBT. Loss of p16 expression was seen in both BdBT and MBT. Cyclin D1 expression was in proportion to the degree of malignancy. Amplification of MDM2, loss of CDKN2A (p16-encoding gene), and amplification of CCND1 (cyclin D1-encoding gene) were confirmed by commercial next-generation sequencing in the case of MBT. CONCLUSIONS: We are the first to report immunohistochemical expression of MDM2 in an MBT. Amplification of MDM2 and loss of p16 expression may have a role in malignant transformation of BT.

Pure Transitional Cell Carcinoma of the Ovary Presenting as Bilateral Complex Cystic Masses in a Premenopausal Woman - Case Report and Review of Literature.

The understanding of ovarian malignancy pathogenesis has greatly increased with identification of varied genomic mutation profiles, which directs the clinical behavior of the tumors. The present case describes the rare subtype of pure transitional cell carcinoma which is no more included in the newer World Health Organization (WHO) classification as the WHO labels it as a type of high-grade serous ovarian cancer with transitional cell differentiation, although in our case no serous component was identified. Hence, with revised classification of ovarian malignancies, it is important to report all rare subtypes in order to understand their biology and behavior.

Malignant Brenner tumor of the ovary: Case series and review of treatment strategies.

Malignant Brenner tumor (MBTs) is a rare histological subtype of epithelial ovarian cancer, accounting for <0.05% of all ovarian neoplasms. As such, current evidence on the treatment of MBTs is predominantly limited to case studies and small case series. To add to existing literature, we performed a retrospective review of 10 cases of MBT diagnosed and treated at a single institution between 1999 and 2018. For the 10 cases included in our cohort, the median age was 64 and the median tumor stage was IIa/IIb. All patients underwent either a primary or interval debulking surgery and achieved an R0 resection per classifications set by the Union for International Cancer Control (UICC). Lymph node dissections were performed on 6 patients and found no evidence of positive nodal disease. 7 patients received platinum-based adjuvant chemotherapy and experienced a median progression-free survival (PFS) of 37 months. Recurrent disease was varied in terms of locoregional versus distant spread, and these patients had largely suboptimal responses to salvage chemotherapy with doxorubicin, gemcitabine, and eribulin. Sites of metastatic disease included the liver, lungs, bone, and brain. While there is no consensus for the optimal treatment of this rare disease, MBTs seem to respond well to adjuvant platinum-taxane treatment after complete surgical resection, consistent with the current management approach of other epithelial ovarian cancers. Recurrent disease is considerably more difficult to manage, and clinicians may consider a wider avenue of treatment options to include hormonal, biologic, and radiation therapies.

Malignant Brenner tumor: Two case reports.

Malignant Brenner tumor (MBT) is a rare ovarian tumor that, given the infrequency of the disease, has not been well documented in the literature. Diagnosing MBT both radiographically and histologically remains a challenge. We report two cases of ovarian MBT, detailing the clinical presentation, radiographic characteristics, and histologic findings with supplementary imaging. Our cases demonstrate the pathologic challenge of histologically diagnosing MBT versus other Brenner tumors and transitional cell carcinoma (TCC) of the ovary.

Malignant Brenner tumor of the ovary: Review and case report.

Ovarian neoplasms are a heterogeneous group of tumors with varying incidence in the general population. The most common are the surface epithelial tumors which include transitional cell tumors. Transitional cell tumors include both transitional cell carcinoma and Brenner tumor. The vast majority of Brenner tumors are benign, often incidental findings; however, malignant Brenner tumors (MBT) do occasionally occur. MBT present similarly to other ovarian neoplasms with abdominal pain and bulk symptoms. On imaging, these tumors demonstrate nonspecific findings. Microscopically, they demonstrate areas of conventional benign Brenner tumor juxtaposed with regions of frank malignancy showing marked cytologic atypia and infiltration. There is no consistent tumor marker for these tumors, but CA-125, CA 72-4 and SCC have been reported in singular instances. Tumors express several immunohistochemical markers of urothelial differentiation including uroplakin III, thrombomodulin, GATA3, p63, as well as cytokeratin 7. The primary treatment modality is surgical excision. Due to their rarity, the precise role and regimen of adjuvant chemo-radiation therapy for MBT has not been established. We herein review a case of MBT with emphasis on primary treatment and treatment of recurrent disease, including the use of adjuvant pelvic radiation, discuss the current state of the literature and standards of practice regarding this malignancy.

Malignant Brenner tumor associated with a germline BRCA2 mutation.

•The first woman with a Malignant Brenner tumor and a BRCA2 mutation is described.•Not all women with epithelial ovarian cancers are referred for genetic counseling.•Women should be referred for genetics regardless of how rare the histology.

Hypercalcemia associated with a malignant brenner tumor arising from a mature cystic teratoma.

A 60-year-old woman presented with abdominal pain and weight loss and was found to have serum calcium of 15.0 mg/dl. Serum parathyroid hormone-related peptide (PTHrP) returned elevated. Imaging suggested bilateral mature cystic teratomas. Her hypercalcemia was treated initially with intravenous saline, as well as intramuscular and subcutaneous calcitonin. She underwent total abdominal hysterectomy with bilateral salpingo-oophorectomy, and final pathology revealed malignant Brenner tumor in association with a mature cystic teratoma. Her postoperative PTHrP returned less than assay, and her total and ionized calcium fell below normal, requiring supplemental calcium and vitamin D. At follow-up one month after discharge, her calcium had normalized. We present the first reported case of hypercalcemia occurring in association with a malignant Brenner tumor. Malignancy-associated hypercalcemia occurs via four principal mechanisms: (1) tumor production of PTHrP; (2) osteolytic bone involvement by primary tumor or metastasis; (3) ectopic activation of vitamin D to 1,25-(OH)(2) vitamin D, and (4) ectopic production of parathyroid hormone. PTHrP-mediated hypercalcemia is the most common mechanism and was responsible in this case. In patients with paraneoplastic hypercalcemia who undergo surgical treatment, close monitoring and management of serum calcium is necessary both pre- and postoperatively.

Nonserous Ovarian Epithelial Tumors.

This review covers the group of relatively uncommon nonserous ovarian epithelial tumors. The authors focus on the group's distinctiveness from the much more common serous tumors and show the similarities across entities. Diagnostic criteria that separate the different entities are currently being debated. Particular problems include the reproducible diagnosis of high-grade endometrioid, transitional cell, mixed epithelial and undifferentiated carcinomas. Furthermore, despite recognition that most malignant mucinous tumors involving ovary represent metastases from extraovarian primary sites, many misdiagnoses still occur. The authors discuss their rationale behind their opinions about these problematic topics.

A case of primary transitional cell carcinoma of the ovary / 대한산부인과학회지

Primary ovarian transitional cell carcinoma (TCC) is extremely rare type of tumor and resembles transitional cell carcinoma of the bladder. Primary ovarian TCC has been classified as a different subtype from malignant Brenner tumor for it's histologic and clinical characteristics. It usually presents at an advanced stage .Though more aggressive than malignant Brenner tumor, it shows more favorable prognosis because of better response to the chemotherapy than other epithelial ovarian carcinomas. We experienced a case of primary ovarian transitional cell carcinoma in a premenopausal woman who underwent staging operation and chemotherapeutic treatment, and herein report the case with a brief review of related literatures.

A case of malignant Brenner tumor developed at an ovary after contralateral oophorectomy / 부인종양

The Brenner tumors of the ovary are uncommon and constitute 1.5-2.5% of all ovarian neoplasms. And their malignant counterparts are rare. Although the first malignant Brenner tumor was described by Von Numers in 1945, only a few malignant Brenner tumors have been reported. The definition and its biologic behavior, and the optimal treatment has not been established. We present a patient who had total abdominal hysterectomy with unilateral salpingooophorectomy due to adenomyosis. The resected ovary had only follicular cysts and the remained ovary was grossly normal . Malignant Brenner tumor developed at the remained ovary 15 years after operation. Operation and adjuvant chemotherapy was applied and patient is alive without evidence of disease. We have experienced a case of malignant Brenner tumor developed at the remained ovary after contralateral oophorectomy with a brief review of literature.

Establishment of a novel malignant Brenner tumer cell line / 대한산부인과학회지

OBJECTIVE: Ovarian cancer is the most lethal disease among gynecologic malignancies. Although many efforts have been made to explore the mechanisms involved in its development, the genetic events in the pathogenesis of ovarian cancer are still unclear. We characterized a cell line (designated OHK) established from a malignant Brenner tumor cell. METHODS: The cells were obtained during the operation of a 43-year-old Korean woman with ovarian cancer. The OHK cells continuously propagated in vitro over a period of about 36 months and, to date, have undergone over 200 passages, without being infected by either Mycoplasma or any bacteria. We measured the doubling time of OHK cells. To investigate the tumorigenecity of OHK, cells were inoculated subcutaneously into the back of nude mice. Several tumor markers were analyzed using culture media and lysates of cytosol. Morphology and ultrastructure were analyzed by phase-contrast microscopy and electron microscopy. OHK was also analyzed for gene mutation, the typing of human leukocyte antigen and Flow cytometric cell cycle analysis and DNA index. RESULTS: They proliferated in a monolayered sheet showing a pavement-like arrangement without suppression by intercellular contacts. They also formed epithelial cell lining in shapes of polymorphism and polygons. Doubling time was 38.4 hour which was relatively slow compared to other cancer cells. Microscopic view revealed intranuclear infoldings which are typical in malignant Brenner tumors. The OHK cells secreted significantly high level of CA 125 into the culture medium. A 215th codon at exon 4 of p53 was mutated to C/C in OHK. BRCA 1 was a wild type and polymorphisms were detected in exons 2, 10, 11, 14 and 17 of BRCA 2. The cells showed aneuploidy with DNA index of 1.589 measured by flow cytometry. When transplanted into nude mice, OHK cells successfully induced tumor which was histopathologically resembled malignant Brenner tumor. CONCLUSION: These results strongly suggest that OHK is a typical cell line of malignant Brenner tumor. This may provide a useful cellular resource for studying the pathogenesis of malignant Brenner tumor.

A Case of Transitional Cell Carcinoma of the Ovary / 대한산부인과학회잡지

Ovarian transitional cell carcinoma (TCC) resembles transitional cell carcinoma of the bladder. As a very rare type of tumor, it accounts for less than 2% of the total incidence of ovarian cancer. Though more aggressive than malignant Brenner tumor, it shows more favorable prognosis because of better response to the chemotherapy than other epithelial ovarian carcinomas. We experienced a case of ovarian TCC in a menopausal woman with a chief complaint of palpable pelvic mass, who underwent staging operation and platinum based (carboplatin-cyclophosphamide) chemotherapeutic treatment, and herein report the case with a brief review of related literatures.

Primary Transitional Cell carcinoma of the Ovary / 대한부인종양콜포스코피학회잡지

Primary transitional cell carcinoma of the ovary is recently recognized, as one of the main types of ovarian carcinoma. Histologically, it is distinguished from malignant Brenner tumor only in the abscence of benign or proliferative Brenner tumor component. primary transitional cell carcinomas are more aggressive than malignant Brenner tumors. However, Primary transitional cell carcinomas have a better response to chemotherapy than other types of ovarian carcinomas. We report a case of primary transitional cell carcinoma presenting as both ovarian masses that developed in a 60-year-old woman with a brief review of literature.

Malignant Brenner Tumor: Report of a case

Brenner tumors constitute about l.5~2.5% of all primary ovarian neoplasms and are almost always benign. It appears to derive from the surface epithelium of the ovary which undergoes metap1asia to form the urothelial-like components. we experienced a case of malignant Brenner tumor with adenocarcinoma and squamous cell carcinoma patterns in a 57-year-old woman. It was partly cystic tumor and contained a 4cm-sized gray yellow, lobulated or papillary solid mass, projecting from the cystic wall. Ultrastructurally, the solid mass was composed of malignant urothelial-like cells with focal glandular differentiation.

Primary Transitional Cell Carcinoma of the Ovary: A case report

Primary ovarian transitional cell carcinoma(TCC) is a recently described, distinct subtype of ovarian carcinoma resembling TCC of the urinary bladder. TCC differs from malignant Brenner tumor(MBT) by absence of benign or proliferative Brenner component and prominent stromal calcification. TCC also represents a high-stage tumor with more aggressive biologic behavior than MBT, but it has a relatively favorable response to chemotherapy. TCC may arise from the pluripotential surface epithelium of the ovary or from the cells with urothelial differentiation, rather than from a benign or proliferative Brenner tumor precursors. We report a case of pure form of primary TCC presenting as a left ovarian mass in 45-year-old woman.